Lenticol -M Mesenchymal Stromal Cells engineered to express Collagen VII for the treatment of RDEB
Dr Waseem Qasim, Professor J McGrath, Francesco Dazzi
Further info A trial is currently underway to test the ability of fibroblasts to provide collagen VII in the skin of patients with RDEB. The trial will provide important information on the safety and feasibility of localised injections of engineered cells into the skin. We now want to prepare for a more generalised approach using bone marrow derived cells called MSCs. This project aims to develop reagents and to test gene engineering of MSCs. It will include production of lentiviral vector and testing in an animal model, using human skin grafts from EB patients.
Deep Sequencing Recessive Dystrophic Epidermolysis Bullosa Squamous Cell Carcinoma
Dr Andrew South (Thomas Jefferson University) and Dr Raymond Cho (Department of Dermatology, University of California)
Patients with recessive dystrophic epidermolysis bullosa (RDEB) frequently develop aggressive, life-threatening cutaneous squamous cell carcinoma (cSCC). Although mechanisms have been proposed to explain why patients suffer this fatal complication, testing such hypotheses requires knowledge of which mutations contribute to the development of RDEB cSCCs. Identifying the mutational landscape of RDEB cSCCs should provide critical insight on how a cancer can develop so quickly in the absence of lifelong sun exposure and DNA damage. Understanding such mechanisms should elucidate modes of prevention and early detection unique to these patients. An increasing number of chemotherapies targeting specific gene mutations are currently in clinical use or development, thus sequencing these cancers may match a known treatment to RDEB patients. This project proposes to sequence 30 RDEB cSCC tumors and matched germ line DNA. This project aims to find tractable therapy options or targets for future development, both clinically and experimentally.